Systems and methods for producing asynchronous neural responses to treat pain and/or other patient conditions

ABSTRACT

Systems and methods for producing asynchronous neural responses to treat pain and/or other patient conditions are disclosed. A method in accordance with a particular embodiment includes selecting a target stimulation frequency that is above a threshold frequency, with the threshold frequency corresponding to a refractory period for neurons of a target sensory neural population. The method can further include producing a patient sensation of paresthesia by directing an electrical signal to multiple sensory neurons of the target sensory neural population at the stimulation frequency, with individual neurons of the sensory neural population completing corresponding individual refractory periods at different times, resulting in an asynchronous sensory neuron response to the electrical signal.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation application of U.S. patent application Ser. No.15/192,914, filed Jun. 24, 2016, no. U.S. patent No. entitled SYSTEMSAND METHODS FOR PRODUCING ASYNCHRONOUS NEURAL RESPONSES TO TREAT PAINAND/OR OTHER PATIENT CONDITIONS, which is a continuation of U.S. patentapplication Ser. No. 14/483,061, filed Sep. 10, 2014, entitled SYSTEMSAND METHODS FOR PRODUCING ASYNCHRONOUS NEURAL RESPONSES TO TREAT PAINAND/OR OTHER PATIENT CONDITIONS, which is a continuation of U.S. patentapplication Ser. No. 13/857,960, filed Apr. 5, 2013, now issued as U.S.Pat. No. 8,849,410, entitled SYSTEMS AND METHODS FOR PRODUCINGASYNCHRONOUS NEURAL RESPONSES TO TREAT PAIN AND/OR OTHER PATIENTCONDITIONS, which is a continuation application of U.S. patentapplication Ser. No. 13/544,727, filed Jul. 9, 2012, now issued as U.S.Pat. No. 8,509,906, entitled SYSTEMS AND METHODS FOR PRODUCINGASYNCHRONOUS NEURAL RESPONSES TO TREAT PAIN AND/OR OTHER PATIENTCONDITIONS, which is a continuation application of U.S. patentapplication Ser. No. 12/362,244, filed Jan. 29, 2009, now issued as U.S.Pat. No. 8,255,057, entitled SYSTEMS AND METHODS FOR PRODUCINGASYNCHRONOUS NEURAL RESPONSES TO TREAT PAIN AND/OR OTHER PATIENTCONDITIONS, which are incorporated herein by reference in theirentireties.

TECHNICAL FIELD

The present disclosure is directed generally to systems and methods forproducing asynchronous neural responses, such as for the treatment ofpain and/or other disorders.

BACKGROUND

Neurological stimulators have been developed to treat pain, movementdisorders, functional disorders, spasticity, cancer, cardiac disorders,and various other medical conditions. Implantable neurologicalstimulation systems generally have an implantable pulse generator andone or more leads that deliver electrical pulses to neurological tissueor muscle tissue. For example, several neurological stimulation systemsfor spinal cord stimulation (SCS) have cylindrical leads that include alead body with a circular cross-sectional shape and one or moreconductive rings spaced apart from each other at the distal end of thelead body. The conductive rings operate as individual electrodes and inmany cases, the SCS leads are implanted percutaneously through a largeneedle inserted into the epidural space, with or without the assistanceof a stylet.

Once implanted, the pulse generator applies electrical pulses to theelectrodes, which in turn modify the function of the patient's nervoussystem, such as altering the patient's responsiveness to sensory stimuliand/or altering the patient's motor-circuit output. In pain treatment,the pulse generator applies electrical pulses to the electrodes, whichin turn can generate sensations that mask or otherwise alter thepatient's sensation of pain. For example, in many cases, patients reporta tingling or paresthesia that is perceived as more pleasant and/or lessuncomfortable than the underlying pain sensation. While this may be thecase for many patients, many other patients may report less beneficialeffects and/or results. Accordingly, there remains a need for improvedtechniques and systems for addressing patient pain.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of an implantable spinal cordstimulation system positioned at the spine to deliver therapeuticsignals in accordance with an embodiment of the present disclosure.

FIG. 2 is a flow diagram illustrating a process for selecting afrequency in accordance with which stimulation is provided to a patientin an embodiment of the disclosure.

FIG. 3 is a flow diagram illustrating a representative process fortreating a patient in accordance with an embodiment of the disclosure.

FIG. 4 is a timing diagram illustrating an electrical therapy signalhaving parameters selected in accordance with a representativeembodiment of the disclosure.

FIG. 5 is a flow diagram illustrating a process for selecting parametersfor delivering multiple electrical signals in accordance with anotherembodiment of the disclosure.

FIG. 6 is a timing diagram illustrating signal delivery parameters fortwo signals delivered in accordance with an embodiment of thedisclosure.

FIG. 7 is a timing diagram illustrating parameters for delivering twosignals in accordance with another embodiment of the disclosure.

FIG. 8 is a timing diagram illustrating a process for delivering threesignals in accordance with still another embodiment of the disclosure.

FIG. 9 is a schematic illustration of an electrode configured to delivertwo signals in accordance with an embodiment of the disclosure.

FIG. 10 is a partially schematic, cross-sectional illustration of apatient's spine illustrating representative locations for implanted leadbodies in accordance with an embodiment of the disclosure.

FIG. 11 is a partially schematic illustration of a lead body configuredin accordance with another embodiment of the disclosure.

FIG. 12 is a partially schematic, cross-sectional illustration of thepatient's spine illustrating representative locations for implanted leadbodies in accordance with still further embodiments of the disclosure.

DETAILED DESCRIPTION A. Overview

The present disclosure is directed generally to systems and methods forproducing asynchronous neural output or responses, such as to treatpain. Specific details of certain embodiments of the disclosure aredescribed below with reference to methods for stimulating a targetneural population or site of a patient, and associated implantablestructures for providing the stimulation. Although selected embodimentsare described below with reference to stimulating the dorsal root and/orother regions of the spinal column to control pain, the leads may insome instances be used for stimulating other neurological structures,and/or other tissue (e.g., muscle tissue). Some embodiments can haveconfigurations, components or procedures different than those describedin this section, and other embodiments may eliminate particularcomponents or procedures. A person of ordinary skill in the relevantart, therefore, will understand that the invention may have otherembodiments with additional elements, and/or may have other embodimentswithout several of the features shown and described below with referenceto FIGS. 1-12 .

A representative method in accordance with a particular embodiment fortreating a patient's pain includes selecting a target stimulationfrequency that is above a threshold frequency. The threshold frequencycorresponds to a refractory period for neurons of a target sensoryneural population. The method can further include producing a patientsensation of paresthesia by directing an electrical signal to multiplesensory neurons of the target sensory neural population at the targetstimulation frequency. Individual neurons of the sensory neuralpopulation can complete corresponding individual refractory periods atdifferent times, resulting in an asynchronous sensory neuron response tothe electrical signals. In at least some embodiments, it is expectedthat this method can produce an enhanced effect for the patient, e.g. asmoother and/or a more pleasant sensation than that resulting fromstandard spinal cord stimulation.

In a further particular embodiment, directing the electrical signal inaccordance with the foregoing method can include initiating theasynchronous sensory neuron response by directing to the target sensoryneural population a generally constant stream of pulses at a frequencygreater than the threshold frequency. The duration of the asynchronoussensory response can then be extended (e.g., beyond an initial period)by directing multiple electrical signals to the target sensory neuralpopulation. These signals can include a first electrical signal havingpulses delivered at a first frequency that is at or above the thresholdfrequency, and a second electrical signal having pulses delivered at asecond frequency, also at or above the threshold frequency. The pulsesof the first and second signals can be interleaved, with individualpulses of the first electrical signal being followed by individualpulses of the second electrical signal, and spaced apart from theindividual pulses of the first electrical signal by a first timeinterval less than the refractory period. Individual pulses of thesecond electrical signal are followed by individual pulses of the firstelectrical signal, and are spaced apart from the individual pulses ofthe first electrical signal by a second time interval that is also lessthan the refractory period.

B. Embodiments of Methods for Applying Neural Stimulation, andAssociated Systems

FIG. 1 schematically illustrates a representative treatment system 100for providing relief from chronic pain and/or other conditions, arrangedrelative to the general anatomy of a patient's spinal cord 191. Thesystem 100 can include a pulse generator 101, which may be implantedsubcutaneously within a patient 190 and coupled to a signal deliveryelement 109. In a representative example, the signal delivery element109 includes a lead body 110 that carries features for deliveringtherapy to the patient 190 after implantation. The pulse generator 101can be connected directly to the lead body 110 or it can be coupled tothe lead body 110 via a communication link 102. As used herein, the termlead body includes any of a number of suitable substrates and/or supportmembers that carry devices for providing therapy signals to the patient190. For example, the lead body 110 can include one or more electrodesor electrical contacts that direct electrical signals into the patient'stissue, such as to provide for patient relief. In other embodiments, thesignal delivery element 109 can include devices other than a lead body(e.g., a paddle) that also direct electrical signals and/or other typesof signals to the patient 190.

The pulse generator 101 can transmit signals to the signal deliveryelement 109 that up-regulate (e.g. stimulate) and/or down-regulate (e.g.block) target nerves. Accordingly, the pulse generator 101 can include amachine-readable (e.g., computer-readable) medium containinginstructions for generating and transmitting suitable therapy signals.The pulse generator 101 and/or other elements of the system 100 caninclude one or more processors, memories and/or input/output devices.The pulse generator 101 can include multiple portions, elements, and/orsubsystems (e.g., for directing signals in accordance with multiplesignal delivery parameters), housed in a single housing, as shown inFIG. 1 , or in multiple housings.

In some embodiments, the pulse generator 101 can obtain power togenerate the therapy signals from an external power source 103. Theexternal power source 103 can transmit power to the implanted pulsegenerator 101 using electromagnetic induction (e.g., RF signals). Forexample, the external power source 103 can include an external coil 104that communicates with a corresponding internal coil (not shown) withinthe implantable pulse generator 101. The external power source 103 canbe portable for ease of use.

In another embodiment, the pulse generator 101 can obtain the power togenerate therapy signals from an internal power source, in addition toor in lieu of the external power source 103. For example, the implantedpulse generator 101 can include a non-rechargeable battery or arechargeable battery to provide such power. When the internal powersource includes a rechargeable battery, the external power source 103can be used to recharge the battery. The external power source 103 canin turn be recharged from a suitable power source (e.g., conventionalwall power).

In still further embodiments, an external programmer (not shown) cancommunicate with the implantable pulse generator 101 via electromagneticinduction. Accordingly, a practitioner can update the therapyinstructions provided by the pulse generator 101. Optionally, thepatient may also have control over at least some therapy functions,e.g., starting and/or stopping the pulse generator 101.

FIG. 2 is a flow diagram illustrating a process 270 for selecting signaldelivery parameters in accordance with an embodiment of the disclosure.Process portion 271 includes identifying a target sensory neuralpopulation. For example, the target sensory neural population caninclude a neural population (e.g., neural fibers) located at the spinalcord. Process portion 272 can include identifying a refractory periodfor neurons of the target neural population. As used herein, therefractory period refers generally to the period of time during which anactivated neuron (e.g., a neuron that has fired an action potential) isunable to fire an additional action potential. The refractory periodincludes an absolute refractory period and a relative refractory period.The absolute refractory period refers generally to the period duringwhich no new action potential can be produced, no matter the strength ofthe electrical signal applied, and the relative refractory period refersgenerally to the period during which a new action potential can beproduced, but the stimulus strength must be increased. Unless otherwisenoted, a refractory period as used herein generally refers to the entireor total refractory period, e.g., the combined absolute refractoryperiod and relative refractory period. The refractory period cancorrespond to an average expected refractory period for a population ofneurons, or to a refractory period of a particular neuron. Therefractory period can be determined based on information obtained from apool of patients or other generalized data, or a practitioner candetermine a patient-specific refractory period. For example, thepractitioner can use generalized refractory period data initially,(e.g., to establish a threshold frequency and a target frequency, asdescribed below) and can then fine-tune the target frequency based onpatient-specific requirements and/or feedback. In at least some cases,the refractory period may vary from one neural population to another. Insuch cases, the practitioner can identify or determine a refractoryperiod for a specific neural population, or base an estimate for therefractory period on an established correspondence or similarity betweenneural populations.

Process portion 273 includes determining a threshold frequency based atleast on part on the refractory period. Generally, process portion 273includes taking the inverse of the refractory period to determine thethreshold frequency. Process portion 274 can include selecting a targetstimulation frequency that is above the threshold frequency. Forexample, the target stimulation frequency can be selected so thatneighboring pulses are spaced apart by less than the total refractoryperiod, but more than the absolute refractory period. In otherembodiments, the target stimulation frequency can be selected so thatneighboring pulses are spaced apart by less than the absolute refractoryperiod. The degree to which the target stimulation frequency exceeds thethreshold frequency can be selected based (at least in part) uponfactors that include the nature of the target sensory neural population,patient-specific feedback, and/or others. In particular embodiments, thetarget stimulation frequency can be about an order of magnitude (e.g.,about a factor of 10) or more above the threshold frequency. In otherembodiments, the target stimulation frequency can be double thethreshold frequency, or another multiple of the threshold frequencygreater than or less than 2, but greater than 1. For example, in aparticular embodiment, the absolute refractory period for A13 fibers hasa value of from about 1 msec. to about 3 msec. (and a relativerefractory period of about 1-2 msec.), corresponding to a frequencyrange of about 200 Hz-1,000 Hz. The corresponding target stimulationfrequency can have a value of 2,000 Hz, 3,000 Hz, 5,000 Hz, 8,000 Hz or10,000 Hz. In a further particular embodiment, it is expected thatfrequencies between 3,000 Hz and 10,000 Hz will produce enhanced patientbenefits. These values are higher than the standard spinal cordstimulation frequency, which is generally from 2 to 1,500 Hz. Theparticular value of the frequency selected for a given patient candepend at least in part on patient feedback (e.g., which frequencyprovides the most pleasant sensation), and/or a target system powerrequirement, with higher frequencies generally corresponding to higherpower requirements. In any of these embodiments, as a result of theselected frequency being greater than the threshold frequency,individual pulses of the electrical signal will be directed both tosensory neurons that are in refractory, and sensory neurons that are inrefractory but excitable. In process portion 275, a stimulation device(e.g., a spinal cord stimulation device) is programmed to deliver theelectrical signal at the target stimulation frequency.

FIG. 3 is a flow diagram of a process 370 for treating a patient.Process portion 371 includes implanting an electrical stimulation deviceproximate to a target sensory neural population e.g., at the patient'sspinal cord. Process portion 372 includes directing an electrical signalto multiple sensory neurons of the target sensory neural population atthe target stimulation frequency. In process portion 373, individualneurons of the sensory neural population complete correspondingindividual refractory periods at different times. This may resultbecause individual neurons can have different individual refractoryperiods based on the size of the neuron and also because thephysiological activation of sensory neurons is not synchronous acrossthe entire population. Process portion 374 includes producing asensation of paresthesia in the patient, resulting from an asynchronoussensory neuron response to the electrical signals. For example, byapplying an electrical signal at a frequency greater than the thresholdfrequency, individual neurons are expected to be exposed to (and respondto) a stimulation pulse very quickly after completing correspondingindividual refractory periods. Because individual neurons are completingindividual refractory periods at different times, the individual neuronsbecome reactivated at different times. This produces an asynchronoussensory neuron response that is expected to have an improved sensationfor the patient. In particular, patients treated with such a stimulationsignal are expected to report a smooth and/or otherwise pleasantsensation, as opposed to a rough, tingly, prickly, and/or othersensation that may not be as pleasant. In addition, it is expected thatsuch signals will not block afferent signals from the target sensoryneural population. Accordingly, in particular embodiments, the patient'sability to perceive other sensations is not expected to be affectedsignificantly or at all. As a result, selecting the target stimulationfrequency in accordance with the foregoing parameters can produce abeneficial result for the patient.

FIG. 4 is a timing diagram illustrating a representative first signal430 in accordance with a particular embodiment of the presentdisclosure. In this embodiment, the signal 430 includes a continuousstring of biphasic, charge-balanced, paired pulses 431 having a pulsewidth PW. Each neighboring pair of anodic and cathodic pulsescorresponds to a cycle 432 having a period P and an associated frequencyF. Because each cycle 432 immediately follows the preceding cycle 432,the signal 430 has no interpulse interval.

As is also shown in FIG. 4 , the frequency F of the signal 430 producesa period P for each cycle 432 that is significantly less than acorresponding refractory period RP. This arrangement is expected toproduce the patient sensations described above with reference to FIG. 3.

In some cases, it may be desirable to reduce the power required todeliver the electrical signal, without significantly reducing theassociated asynchronous neural response. One approach to achieving thisresult is to deliver multiple electrical signals, for example, twoelectrical signals, that together produce an asynchronous neuralresponse, but with less power than is required to produce the continuousstream of pulses shown in FIG. 4 . FIG. 5 illustrates a representativemethod 570 for producing such a result. The method 570 includesselecting first electrical signal parameters (process portion 571) thatcan include a first frequency, first pulse width, first interpulseinterval, first burst frequency, first burst width, first interburstinterval, and first intensity. The frequency, pulse width, andinterpulse interval of the first signal are described above withreference to FIG. 4 . The burst frequency refers to the frequency atwhich groups of pulses are delivered to the patient, and the burst widthrefers to the time period over which any particular group of pulses isdelivered. The interburst interval refers to the time period betweenbursts, and the intensity refers to the amplitude (e.g., voltage and/orcurrent) or intensity of the pulses. In a representative example, thepulses are provided at current-controlled intensity level of from about0.1 mA to about 20 mA, and, more particularly, about 0.5 mA to about 5.0mA, with a varying voltage of up to about 15 volts, and a frequency ofabout 10,000 Hz. Values toward the higher ends of the foregoing rangesmay be used in particular embodiments, e.g., when sensory subcutaneousnerves and/or other sensory and/or motor peripheral nerves (as opposedto spinal nerves) form the target neural population. In a furtherrepresentative example, sequential bursts can be separated from eachother by less than one second, and the overall duty cycle of the firstsignal alone (or the first and second signals together) can be about50%.

Process portion 572 includes selecting corresponding parameters for thesecond electrical signal. Process portion 573 includes selecting a phaseshift or offset between pulses of the first signal and pulses of thesecond signal. In process portion 574, the first and second electricalsignals are directed to a target neural population. Optionally, theprocess 570 can include varying the signal delivery parameters (processportion 575), for example, by varying the first interpulse interval witha constant phase shift between pulses of the first signal and pulses ofthe second signal, or by varying the phase shift with a constant firstinterpulse interval. Examples of representative wave forms selected inaccordance with the process 570 are described below with reference toFIGS. 6-8 .

FIG. 6 is a timing diagram illustrating wave forms for two electricalsignals, shown as a first electrical signal 630 a and a secondelectrical signal 630 b. The first electrical signal 630 a includesfirst cycles 632 a, each of which includes a first pulse 631 a having apulse width PW1. Individual first cycles 632 a have a first period P1.The second electrical signal 630 b includes multiple second cycles 632b, each of which includes a second pulse 632 b having a second pulsewidth PW2. Individual second cycles 632 b have a second period P2.

In a particular embodiment, each second cycle 632 b of the second signal630 b follows a corresponding first cycle 632 a of the first signal 630a, and is spaced apart from the first cycle 632 a by an offset or phaseshift O. In particular embodiments, the offset O can have a constantvalue, so that the first and second frequencies F1, F2 are equal. Inother embodiments, the offset O can vary, which can prolong theeffectiveness of the therapy. It is believed that one possible mechanismby which the therapy effectiveness can be prolonged is by reducing thepatient's maladaptive response, e.g., by reducing a tendency for thepatient's central nervous system to lessen its response to the effectsof a non-varying signal over time. In still further embodiments, it isexpected that the practitioner can reduce the patient's maladaptiveresponse without varying signal delivery parameters, and/or via atreatment regimen that includes more than two electrical signals or onlya single electrical signal. For example, in at least some embodiments,applying a single, constant frequency signal (e.g., as shown in FIG. 4 )so as to produce an asynchronous neural response, can reduce themaladaptive response of the patient's central nervous system, e.g., whencompared with a signal that produces a synchronous neural response.

The combination of the first signal 630 a and the second signal 630 bproduces a combined period PC corresponding to the first period P1 plusthe offset O. In a particular aspect of this embodiment, the combinedperiod PC is selected to be smaller than the refractory period RP.However, the first frequency F1 may be selected to be slower than thecorresponding total refractory period. If the first signal 630 a alonewere provided to the patient in accordance with these parameters, itwould not likely produce an asynchronous neural response. However, thesecond signal 630 b can supplement the effects of the first signal 630a. In particular, the second pulses 631 b are delivered in a manner thatactivates neurons that may come out of their refractory periods afterthe preceding first pulse 631 a. This is expected to be the case becausethe combined period PC is less than the refractory period RP. Forexample, the combined period PC can be a suitable fraction (e.g.,one-half or one-third) of the total refractory period RP. These valuescan be less than the total refractory period, but greater than theabsolute refractory period. In a particular embodiment, the totalrefractory period RP can have a value of about 2-4 msec, and the firstand second frequencies F1, F2 can have a value of from about 250 Hz toabout 500 Hz. The combined period PC can have a value of from about 50μsec. to about 300 μsec. and in a particular embodiment, about 100 μsec.

In operation, the first and second signals 630 a, 630 b may be appliedto the patient after the constant pulses described above with referenceto FIG. 4 are applied. Accordingly, the constant pulse pattern shown inFIG. 4 can be used to establish an initial asynchronous neural response,for example, over a time period of several microseconds to severalseconds, e.g., several milliseconds. This asynchronous response periodcan be extended by the first and second signals 630 a, 630 b, withoutexpending the amount of power required to produce a continuous stream ofpulses over the same period of time. The power savings can resultbecause the combination of the first and second signals 630 a, 630 bproduces a quiescent period Q during which no pulses are applied to thepatient. In general, it is expected that the quiescent period Q will beless than or equal to the refractory period RP. As a result, the patientbenefit is expected to at least approach the benefit achieved with theconstant stream of pulses shown in FIG. 4 . For example, in a particularembodiment, it is expected that the patient can achieve the same ornearly the same benefit whether the stimulation is in the form of acontinuous stream of pulses at 3 kHz, or two overlaid sets ofspaced-apart pulses, each provided at less than 1.5 kHz, with the latterstimulation requiring less power than the former.

In at least some embodiments, the amplitude of the second signal 630 bmay be greater than that of the first signal 630 a. It is expected thatthe increased amplitude of the second signal 630 b may be more effectiveat activating neurons that are in a relative refractory state ratherthan an absolute refractory state, thus reducing the number of neuronsavailable to fire during the quiescent period Q. In general, it isexpected that using two signals to achieve the foregoing pulse-to-pulseamplitude variation is more readily achievable with two overlaid signalsthan with a single signal, at least for particular stimulationparameters (e.g., at high frequencies). Paired signals with differentamplitudes can also more readily activate smaller Aß fibers. In general,the signals are preferentially directed to Aß fibers over C fibers. Ingeneral, the signals are also preferentially directed so as to avoidtriggering a muscle response. In addition to, or in lieu of, theincreased amplitude, the second signal 630 b can have pulses with asecond pulse width PW2 greater than the first pulse width PW1. Theparticular values of the signal amplitude, pulse width and/or otherparameters can be selected based at least in part on patient feedback.In any of these embodiments, this arrangement can further extend theasynchronous neural response established by the initial constant pulsepattern described above.

FIG. 7 is a timing diagram illustrating wave forms for two electricalsignals, shown as a first electrical signal 730 a and a secondelectrical signal 730 b, having parameters selected in accordance withanother embodiment of the disclosure. The two electrical signals 730 a,730 b are generally similar to the corresponding first and secondelectrical signals 630 a, 630 b described above with reference to FIG. 6, except that the first frequency F1 and the second frequency F2 bothvary, as indicated by frequencies F1A-F1C and F2A-F2C. For example, thefirst frequency F1 initially increases (as pulses become closertogether) and then decreases. The second frequency F2 also decreases andthen increases. In a particular aspect of this embodiment, the offset orphase shift O between pulses of the first electrical signal 730 a andpulses of the second electrical signal 730 b remains constant despitethe changes in the first and second frequencies F1, F2. In some cases,this can produce a varying pulse width PW2 for the second signal 730 b.For example, the second pulse of the second signal 730 b shown in FIG. 7has a reduced pulse width PW2 compared with the pulse width of eitherthe first or third pulse, in order to fit between the second and thirdpulses of the first signal 730 a. This arrangement can prevent thepulses of the two signals 730 a, 730 b from overlapping each other. Onepotential advantage of the varying first and second electrical signals730 a, 730 b shown in FIG. 7 is that this arrangement can reduce thelikelihood for the patient to develop a maladaptive response to aconstant set of signals, while still producing an asynchronous patientresponse, with a reduced power requirement, as discussed above withreference to FIG. 6 .

In other embodiments, the patient can receive stimulation from more thantwo signals. For example, as shown in FIG. 8 , the patient can receivethree electrical signals, shown as a first electrical signal 830 a, asecond electrical signal 830 b, and a third electrical signal 830 c.Pulses of the second electrical signal 830 b can be offset fromcorresponding pulses of the first electrical signal 830 a by a firstoffset O1, and pulses of the third electrical signal 830 c can be offsetfrom pulses of the second electrical signal 830 b by a second offset O2.By superposing the three electrical signals, the patient can feelsensations generally similar to those described above with reference toFIG. 6 or 7 , with a power savings similar in principle (though perhapsnot value) to those described above. In particular, the superposition ofthree signals may provide a smoother effect for the patient withslightly less power savings than are expected from superposing twosignals.

FIG. 9 is a partial schematic illustration of a representative lead body110 coupled to a controller 101 in accordance with a particularembodiment of the disclosure. In this embodiment, the lead body 110includes eight electrodes 112 a-112 h, and the controller 101 includestwo channels, CH1 and CH2. A cathodal signal is applied from the firstchannel CH1 to the third electrode 112 c, and an anodal signal isapplied from the first channel CH1 to the second and fourth electrodes112 b, 112 d. The second channel CH2 applies a cathodal signal to thefourth electrode 112 d, and an anodal signal to the second and fifthelectrodes 112 b, 112 e. In one aspect of this embodiment, at least oneof the electrodes to which the second channel CH2 is coupled isdifferent than the electrodes to which the first channel CH1 is coupled.Accordingly, the portion of the overall target neural populationreceiving the pulses from the second channel CH2 can be different than(though perhaps overlapping with) the portion of the target neuralpopulation receiving pulses from the first channel CH1. It is expectedthat in at least some embodiments this will increase the number ofneurons at the overall target neural population that respondasynchronously. In addition to or in lieu of this effect, it is expectedthat the electrical field produced by the second channel CH2 will differmore significantly from that produced by the first channel CH1 when itis produced by a different set of electrodes, which can also increasethe likelihood of an asynchronous neural response. In other embodiments,signals applied to the channels can be varied in other manners, inaddition to or in lieu of the foregoing arrangement, including but notlimited to switching individual electrodes from cathodic to anodic orvice versa.

FIG. 10 is a cross-sectional illustration of the spinal cord 191 and anadjacent vertebra 195 (based generally on information from Crossman andNeary, “Neuroanatomy,” 1995 (publ. by Churchill Livingstone)), alongwith selected representative locations for representative lead bodies110 (shown as lead bodies 110 a-110 d) in accordance with severalembodiments of the disclosure. The spinal cord 191 is situated between aventrally located vertebral body 196 and the dorsally located transverseprocess 198 and spinous process 197. Arrows V and D identify the ventraland dorsal directions, respectively. In particular embodiments, thevertebra 195 can be at T10 or T11 (e.g., for axial low back pain or legpain) and in other embodiments, the lead bodies can be placed at otherlocations. The spinal cord 191 itself is located within the dura mater199, which also surrounds portions of the nerves exiting the spinal cord191, including the dorsal roots 193 and dorsal root ganglia 194. Thelead body is generally positioned to preferentially stimulate tactilefibers and to avoid stimulating fibers associated with nociceptive paintransmission. In a particular embodiment, a lead body 110 a can bepositioned centrally in a lateral direction (e.g., aligned with thespinal cord midline 189) to provide signals directly to the spinal cord191. In other embodiments, the lead body can be located laterally fromthe midline 189. For example, the lead body can be positioned just offthe spinal cord midline 189 (as indicated by lead body 110 b), and/orproximate to the dorsal root 193 or dorsal root entry zone 188 (e.g.,1-4 mm from the spinal cord midline 189, as indicated generally by leadbody 110 c), and/or proximate to the dorsal root ganglion 194 (asindicated by lead body 110 d). Other suitable locations for the leadbody 110 include the “gutter,” also located laterally from the midline189, and the dorsal root entry zone. In still further embodiments, thelead bodies may have other locations proximate to the spinal cord 191and/or proximate to other target neural populations e.g., laterally fromthe midline 189 and medially from the dorsal root ganglion 194.

FIG. 11 is a partially schematic, side elevation view of a lead body 110configured in accordance with another embodiment of the disclosure. Thelead body 110 can include a first or distal portion 111 a, a second orproximal portion 111 b, and an intermediate third portion 111 c locatedbetween the first and second portions 111 a, 111 b. The first portion111 a can carry signal delivery electrodes 112, or other featuresconfigured to deliver therapeutic signals to the patient. The secondportion 111 b can include connection terminals 113 or other featuresconfigured to facilitate communication with the implantable pulsegenerator 101 (FIG. 1 ). The third portion 111 c can include a link,e.g., an electrical link 108 having multiple wires 114 that providesignal communication between the connection terminals 113 of the secondportion 111 b and the signal delivery electrodes 112 of the firstportion 111 a.

The first portion 111 a can include signal delivery electrodes 112 thathave an annular or ring shape and are exposed at the outercircumferential surface of the first portion 111 a, as shown in FIG. 11. In other embodiments, the signal delivery electrodes 112 can haveother configurations, e.g., the electrodes 112 can have a flat or curveddisc shape. The first portion 111 a can have an overall diameter D1which is sized to allow the first portion 111 a to pass through thelumen of a delivery catheter or other delivery device. The first portion111 a can also include a first fixation device 115 a to secure or atleast partially secure the first portion 111 a in position at a targetsite. In a particular embodiment, the first fixation device 115 a caninclude one or more tines, or an annular cup that faces proximally(rightward as shown in FIG. 11 ) to resist axial motion. In otherembodiments, the first fixation device 115 a can include other features.

The second portion 111 b can include the connection terminals 113described above, and can have an overall diameter D2. In a particularembodiment, the diameter D2 of the second portion of 111 b can beapproximately the same as the diameter D1 of the first portion of 111 a.The second portion 111 b can include a second fixation device 115 b, forexample, one or more sutures 106 that secure or at least partiallysecure the second portion 111 b in position. Each of the first andsecond portions 111 a, 111 b can include rounded, convex externalsurfaces 105 (e.g., at the proximal end of the first portion 111 aand/or at the distal end of the second portion 111 b) that are exposedto patient tissue and, due to the rounded shapes of these surfaces,facilitate moving the lead body 110 in the patient's body. The thirdportion 111 c can have a diameter D3 that is less than the diameters D1,D2 of the first and second portions 111 a, 111 b, and a stiffness lessthan a stiffness of the first and second portions 111 a, 111 b.Accordingly, the third portion 111 c can be flexible enough to allow thesecond portion 111 b to move without disturbing the position of thefirst portion 111 a. Further details of the lead body 110 shown in FIG.11 are included in pending U.S. patent application Ser. No. 12/129,078,filed May 29, 2008 and incorporated herein by reference.

FIG. 12 is a cross-sectional illustration of the spinal cord 191 and anadjacent vertebra 195 along with selected representative locations forrepresentative lead bodies 110 generally similar to those describedabove with reference to FIG. 11 and shown in FIG. 12 as lead bodies 110a-110 d. In each of the foregoing representative locations, the firstportion 111 a of the lead body 110 can be positioned epidurally (orsubdurally) proximate to a target neural population at the spinal cord191 while the second portion 111 b is positioned radially outwardly fromthe spinal cord 191, and while the third portion 111 c provides aflexible coupling between the first and second portions. The firstportion 111 a can be positioned relative to the spinal cord 191 atlocations generally similar to those described above with reference toFIG. 10 .

In a particular embodiment, the practitioner can use an automated (e.g.,computer-implemented) or semi-automated feedback technique to select theparticular frequency or frequencies of signals applied to a patient. Inone aspect of this embodiment, treatment leads can be placed at any ofthe locations shown in FIG. 10 or 12 in the patient's lower back region,for example, at T10. The practitioner can also outfit the patient withone or more diagnostic leads (e.g., epidural recording leads) located atthe gutter, but at a superior position along the spine. For example, thepractitioner can position two epidural recording leads in the gutter,one on each side of the midline, at a cervical location. The diagnosticleads are not expected to discriminate between action potentials fromindividual neurons, but rather can record an overall action potentialsum. At low stimulation frequencies, in response to which the neuronpopulation generates synchronous action potentials, the recorded signalstrength of the compound action potential is expected to be higher thanwhen the patient produces asynchronous responses at higher frequencies,in which the recorded signal will have a lower signal strengthindicating fewer additive action potentials. Accordingly, in oneembodiment, the practitioner can increase the frequency of the signalsapplied to the treatment leads, while observing the amplitude of thesummed compound action potential response recorded by the recordingleads. When the detected response decreases, this can indicate to thepractitioner that the patient is generating asynchronous actionpotentials. This information can be used alone or in combination with apatient response to select a longer term stimulation frequency. In aparticular embodiment, the practitioner can start at a low frequency(e.g., about 40 Hz) and, using an automated program, increase thefrequency of the stimulation applied to the patient up to a level ofabout 10,000 Hz. The program can then automatically decrease thefrequency in accordance with one or more set increments until thedetected response increases to or changes by a threshold level (whichthe program can detect automatically), and/or the patient indicates achange. The patient's reported change may include an indication that thepatient's perceived sensation is no longer smooth and is instead rough,or otherwise less desirable.

In other embodiments, other aspects of the foregoing operation can beautomated. For example, the system can automatically identify a baselinesignal strength corresponding to a synchronous response. In a particularembodiment, the baseline signal strength can be the signal strengthrecorded when the patient is stimulated at 40 Hz or another lowfrequency. As the system automatically increases the stimulationfrequency to identify an appropriate frequency for eliciting anasynchronous response, it compares the recorded signal strengths withthe baseline level. If the recorded signal strength is equal to orhigher than the baseline level, the patient response is identified as asynchronous response. If the recorded signal strength is lower than thebaseline level, then the patient response is identified as asynchronousor transitioning to asynchronous. At this point, the system canautomatically vary the frequency (increasing and/or decreasing) in aclosed loop manner to identify a target frequency (e.g., an optimumfrequency) that the patient will receive during therapy. In a particularembodiment, the target frequency is the frequency that produces the mostasynchronous patient response.

One feature of many of the foregoing embodiments described above is theapplication of one or more electrical signals to the patient's neuraltissue that produce an asynchronous response. As described above, it isexpected that an asynchronous response will produce a smoother orotherwise more pleasant patient sensation than standard spinal cordstimulation, while still masking or otherwise beneficially altering painsignals. In addition, particular embodiments are expected to reducepower consumption by providing intermittent or otherwise spaced-apartsignals that are nevertheless timed to trigger an asynchronous patientresponse. By reducing the power consumption of the device, theseembodiments can decrease the frequency with which the patient rechargesthe implanted stimulator, and/or decrease the frequency with which anon-rechargeable battery within the implanted stimulation must bereplaced. The intermittent signal may also produce other patientbenefits, possibly including an increase in the term over which thetherapy is effective.

From the foregoing, it will be appreciated that specific embodiments ofthe disclosure have been described herein for purposes of illustration,but that various modifications may be made without deviating from theinvention. For example, the wave forms of the electrical signals appliedto the patient may have characteristics other than those specificallyshown and described above. In a particular example, the wave forms mayinclude pulses other than square wave pulses. In other embodiments, theleads or other signal delivery devices may have configurations otherthan those specifically shown and described above. Furthermore, whilecertain embodiments were described in the context of spinal cordstimulation, generally similar techniques may be applied to other neuralpopulations in other embodiments using similar and/or modified devices.For example, stimulation signals selected to produce an asynchronouspatient response can be applied subcutaneously to peripheral nerves.Such nerves can include occipital nerves, which can be stimulated toaddress headaches and/or facial and/or neck pain, and/or peripheralnerves at the lower back to address lower back pain. In still furtherembodiments, the stimulation signals can be applied to neuralpopulations to produce an asynchronous response that addresses patientconditions other than pain. In another embodiment, such signals can beapplied to the autonomic nervous system, e.g., to the splenic nerve toaddress obesity. In any of the foregoing cases, the refractory periodsand threshold frequencies may differ from those associated with spinalcord stimulation, but the methodologies used to select the targetstimulation frequency can be generally the same or similar.

Certain aspects of the invention described in the context of particularembodiments may be combined or eliminated in other embodiments. Forexample, a given signal delivery protocol may include different signalsat different times during a treatment regimen, with the signals havingcharacteristics generally similar to any of those described above withreference to FIGS. 4 and 6-8 . Characteristics of particular signals(e.g., the first signal) may be applied to other signals (e.g., thesecond signal, and/or a continuous pulse stream, such as that shown inFIG. 4 ). Further, while advantages associated with certain embodimentshave been described in the context of those embodiments, otherembodiments may also exhibit such advantages. Not all embodiments neednecessarily exhibit such advantages to fall within the scope of thepresent disclosure. Accordingly, the invention can include otherembodiments not specifically shown or described above.

We claim:
 1. A method of treating pain in a patient, comprising:directing an electrical signal having a first parameter value to thepatient's spinal cord region, via an implanted signal delivery element,wherein the electrical signal induces paresthesia in the patient;measuring a neural response evoked by the electrical signal; based atleast in part on the neural response, adjusting the first parametervalue to a second parameter value, wherein the second parameter value isdifferent than the first parameter value; and iteratively repeating theprocesses of directing, measuring, and adjusting until the electricalsignal induces a smoother and/or more pleasant sensation in the patient.2. The method of claim 1 wherein the smoother and/or more pleasantsensation is correlated with an asynchronous neural response in thepatient.
 3. The method of claim 2 wherein measuring the neural responseevoked by the electrical signal includes measuring an amplitude of acompound action potential representing a sum of individual actionpotentials, and wherein the asynchronous neural response is evidenced bya reduction in the amplitude of the compound action potential.
 4. Themethod of claim 1 wherein the smoother and/or more pleasant sensationresults from the asynchronous neural response.
 5. The method of claim 1wherein the parameter value is a frequency of the electrical signal, andwherein adjusting the first parameter value to the second parametervalue includes increasing the frequency of the electrical signal.
 6. Themethod of claim 5 wherein increasing the frequency includes increasingthe frequency by a preset increment until the electrical signal inducesthe smoother and/or more pleasant sensation.
 7. The method of claim 1wherein measuring the neural response includes measuring the neuralresponse via one or more sensors implanted proximate the patient'sspinal cord.
 8. The method of claim 1 wherein the processes ofdirecting, measuring, adjusting, and iteratively repeating are performedautomatically until the electrical signal induces a smoother and/or morepleasant sensation in the patient.
 9. A method of treating pain in apatient, comprising: programming a pulse generator to: direct anelectrical signal having a first parameter value to the patient's spinalcord region via an implanted signal delivery element, wherein theelectrical signal induces paresthesia in the patient; receive, via asensor, a signal corresponding to a neural response evoked by theelectrical signal; based at least in part on the received signal, adjustthe first parameter value to a second parameter value, wherein thesecond parameter value is different than the first parameter value; andautomatically and iteratively repeat the processes of directing,receiving, and adjusting until the electrical signal induces a smootherand/or more pleasant sensation in the patient.
 10. The method of claim 9wherein the smoother and/or more pleasant sensation is correlated withan asynchronous neural response in the patient.
 11. The method of claim10 wherein the received signal is indicative of an amplitude of acompound action potential representing a sum of individual actionpotentials, and wherein the asynchronous neural response is evidenced bya reduction in the amplitude of the compound action potential.
 12. Themethod of claim 9 wherein the smoother and/or more pleasant sensationresults from the asynchronous neural response.
 13. The method of claim 9wherein the parameter value is a frequency of the electrical signal, andwherein programming the pulse generator to adjust the first parametervalue to the second parameter value includes programming the pulsegenerator to increase a frequency of the electrical signal.
 14. Themethod of claim 13 wherein programming the pulse generator to increasethe frequency includes programming the pulse generator to increase thefrequency by a preset increment until the electrical signal induces thesmoother and/or more pleasant sensation.
 15. The method of claim 9wherein programming the pulse generator to receive the signal via asensor includes programming the pulse generator to receive the signalvia a sensor implanted proximate the patient's spinal cord.
 16. A spinalcord stimulation treatment system, comprising: a pulse generator; and animplantable signal delivery element coupleable to the pulse generatorand configured to be implanted at or proximate a spinal cord of thepatent; wherein, in operation, the pulse generator: directs anelectrical signal having a first parameter value to the patient's spinalcord region via the implanted signal delivery element, wherein theelectrical signal induces paresthesia in the patient; receives, via asensor, a signal corresponding to a neural response evoked by theelectrical signal; based at least in part on the received signal,adjusts the first parameter value to a second parameter value, whereinthe second parameter value is different than the first parameter value;and automatically and iteratively repeats the processes of directing,receiving, and adjusting until the electrical signal induces a smootherand/or more pleasant sensation in the patient.
 17. The system of claim16, further comprising the sensor, wherein the sensor is configured tobe implanted proximate the spinal cord of the patient to measure theneural response evoked by the electrical signal.
 18. The system of claim16 wherein the pulse generator includes a machine-readable medium havinginstructions that, when executed, cause the system to perform theoperations of directing, receiving, adjusting, and iterativelyrepeating.
 19. The system of claim 16 wherein the pulse generator isimplantable.
 20. The system of claim 16 wherein the smoother and/or morepleasant sensation is correlated with an asynchronous neural response inthe patient.
 21. The system of claim 20 wherein the received signal isindicative of an amplitude of a compound action potential representing asum of individual action potentials, and wherein the asynchronous neuralresponse is evidenced by a reduction in the amplitude of the compoundaction potential.
 22. The system of claim 16 wherein the smoother and/ormore pleasant sensation results from the asynchronous neural response.23. The system of claim 16 wherein the parameter value is a frequency ofthe electrical signal, and wherein the operation of adjusting the firstparameter value to the second parameter value includes increasing afrequency of the electrical signal.
 24. The system of claim 23 whereinthe operation of increasing the frequency includes increasing thefrequency by a preset increment until the electrical signal induces thesmoother and/or more pleasant sensation.